Sarcopenia and frailty in decompensated cirrhosis Tandon, Puneeta; Montano-Loza, Aldo J.; Lai, Jennifer C. ...
Journal of hepatology,
July 2021, 2021-07-00, 20210701, Volume:
75, Issue:
Suppl 1
Journal Article
Peer reviewed
Open access
In patients with decompensated cirrhosis, sarcopenia and frailty are prevalent. Although several definitions exist for these terms, in the field of hepatology, sarcopenia has commonly been defined as ...loss of muscle mass, and frailty has been broadly defined as the phenotypic manifestation of the loss of muscle function. Prompt recognition and accurate assessment of these conditions are critical as they are both strongly associated with morbidity, mortality, poor quality of life and worse post-liver transplant outcomes in patients with cirrhosis. In this review, we describe the complex pathophysiology that underlies the clinical phenotypes of sarcopenia and frailty, their association with decompensation, and provide an overview of tools to assess these conditions in patients with cirrhosis. When available, we highlight data focusing on patients with acutely decompensated cirrhosis, such as inpatients, as this is an area of unmet clinical need. Finally, we discuss management strategies to reverse and/or prevent the development of sarcopenia and frailty, which include adequate nutritional intake of calories and protein, as well as regular exercise of at least moderate intensity, with a mix of aerobic and resistance training. Key knowledge gaps in our understanding of sarcopenia and frailty in decompensated cirrhosis remain, including best methods to measure muscle mass and function in the inpatient setting, racial/ethnic variation in the development and presentation of sarcopenia and frailty, and optimal clinical metrics to assess response to therapeutic interventions that translate into a reduction in adverse outcomes associated with these conditions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
AIM To investigate the impact of physical frailty on risk of hospitalisation in cirrhotic patients on the liver transplant waitlist.METHODS Cirrhotics listed for liver transplantation at a single ...centre underwent frailty assessments using the Fried Frailty Index, consisting of grip strength, gait speed, exhaustion, weight loss, and physical activity. Clinical and biochemical data including MELD score as collected at the time of assessment. The primary outcome was number of hospitalised days per year; secondary outcomes included incidence of infection. Univariable and multivariable analysis was performed using negative binomial regression to associate baseline parameters including frailty with clinical outcomes and estimated incidence rate ratios(IRR). RESULTS Of 587 cirrhotics, 64% were male, median age(interquartile range) was 60(53-64) years and MELD score was 15(12-18). Median Fried Frailty Index was 2(1-3); 31.6% were classified as frail(fried frailty ≥ 3). During 12 mo of follow-up, 43% required at least 1hospitalisation; 38% of which involved major infection.107/184(58%) frail and 142/399(36%) non-frail patients were hospitalised at least once(P < 0.001). In univariable analysis, Fried Frailty Index was associated with total hospitalisation days per year(IRR = 1.51,95%CI: 1.28-1.77; P ≤ 0.001), which remained significant on multivariable analysis after adjustment for MELD, albumin, and gender(IRR for frailty of 1.21,95%CI: 1.02-1.44; P = 0.03). Incidence of infection was not influenced by frailty.CONCLUSION In cirrhotics on the liver transplant waitlist, physical frailty is a significant predictor of hospitalisation and total hospitalised days per year, independent of liver disease severity.
Women with cirrhosis awaiting liver transplantation (LT) experience higher rates of waitlist mortality than men; it is unknown whether practices surrounding delisting for being “too sick” for LT ...contribute to this disparity beyond death alone. We conducted an analysis of patients listed for LT in the United Network for Organ Sharing/Organ Procurement and Transplantation Network not receiving exception points from May 1, 2007 to July 1, 2014 with a primary outcome of delisting with removal codes of “too sick” or “medically unsuitable.” A total of 44 388 patients were included; 4458 were delisted for being “too sick” for LT. Delisting was more frequent in women (11% vs 9%, P < .001). Compared to delisted men, delisted women differed in age (58 vs 57), non–hepatitis C virus listing diagnoses (69% vs 56%), hepatic encephalopathy (36% vs 31%), height (161.9 vs 177.0 cm), private insurance (47% vs 52%), and Karnofsky performance status (60 vs 70) (P < .001 for all). There were no differences in Model for End‐Stage Liver Disease including serum sodium and Child Pugh Scores. A competing risk analysis demonstrated that female sex was independently associated with a 10% (confidence interval 2%‐18%) higher risk of delisting when accounting for rates of death and transplantation and adjusting for confounders. This study demonstrates a significant disparity in delisting practices by sex, highlighting the need for better assessments of sickness, particularly in women.
In this analysis of all waitlist candidates in the United States from 2007 to 2014, the investigators demonstrate significant disparities in delisting practices by sex, highlighting the need for better assessments of sickness, particularly in women.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cirrhosis is characterized by sarcopenia and malnutrition, leading to progressive functional decline. We aimed to objectively measure functional decline in patients with cirrhosis awaiting liver ...transplantation and its association with waiting list mortality. Consecutive adults listed for liver transplantation with laboratory Model for End‐Stage Liver Disease (MELD) ≥12 at a single center underwent functional status assessments at every outpatient visit using the Short Physical Performance Battery (0 = impaired to 12 = robust), consisting of gait, chair stands, and balance tests. Joint linear time‐to‐event analyses modeled the simultaneous impact of the longitudinal trajectory of physical function on waiting list mortality (=death or delisted for being too sick for liver transplantation). Included were 309 liver transplantation candidates. Median laboratory MELD was 15, serum albumin was 3.0 g/dL, 28% had ascites, 18% had hepatic encephalopathy, and 83% were Child class B or C. At a median follow‐up of 14 months, 15% died or were delisted and 28% underwent liver transplantation. Average physical function worsened per 3 months on the waiting list: −0.38 kg in grip strength, −0.05 meters/second in gait, 0.03 seconds in chair stands, and −0.16 Short Physical Performance Battery points. In joint models of longitudinal trajectories of physical function and waiting list mortality adjusted for MELD‐Na, albumin, hepatocellular carcinoma, and baseline physical function, the longitudinal trajectories of each physical function measure were significantly associated with waiting list mortality: grip (hazard ratio = 0.89, 95% confidence interval 0.83‐0.95), gait (hazard ratio = 0.72, 95% confidence interval 0.62‐0.84), chair stands (hazard ratio = 1.17, 95% confidence interval 1.09‐1.25), and Short Physical Performance Battery <10 (hazard ratio = 1.45, 95% confidence interval 1.15‐2.20). Conclusion: Liver transplantation candidates experience significant functional decline on the waiting list, despite modest wait time and low baseline MELD; decline in physical function is associated with an increased risk of death or delisting, independent of liver disease severity. (Hepatology 2016;63:574–580)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Physical frailty after liver transplantation Lai, Jennifer C.; Segev, Dorry L.; McCulloch, Charles E. ...
American journal of transplantation,
August 2018, Volume:
18, Issue:
8
Journal Article
Peer reviewed
Open access
Frailty is prevalent in liver transplant candidates, but little is known of what happens to frailty after liver transplantation. We analyzed data for 214 adult liver transplant recipients who had ≥1 ...frailty assessment using the Liver Frailty Index (LFI) at 3‐ (n = 178), 6‐ (n = 139), or 12‐ (n = 107) months posttransplant (higher values=more frail). “Frail” and “robust” were defined as LFI ≥4.5 and <3.2. Median pre–liver transplant LFI was 3.7, and was worse at 3 months (3.9; P = .02), similar at 6 months (3.7; P = .07), and improved at 12 months (3.4; P < .001). The percentage who were robust pre‐ and 3‐, 6‐, and 12‐months posttransplant were 25%, 14%, 28%, and 37%; the percentage frail were 21%, 21%, 10%, and 7%. In univariable analysis, each 0.1 pretransplant LFI point more frail was associated with a decreased odds of being robust at 3‐ (odds ratio OR 0.75), 6‐ (OR 0.77), and 12‐months (OR 0.90) posttransplant (P ≤ .001), which did not change substantially with multivariable adjustment. In conclusion, frailty worsens 3 months posttransplant and improves modestly by 12 months, but fewer than 2 of 5 patients achieve robustness. Pretransplant LFI was a potent predictor of posttransplant robustness. Aggressive interventions aimed at preventing frailty pretransplant are urgently needed to maximize physical health after liver transplantation.
Physical frailty only modestly improves after liver transplantation and is most strongly predicted by pretransplant physical frailty status, suggesting the need for structured interventions aimed at preventing pretransplant physical frailty to maximize physical health after liver transplantation. See Maddur and Levitsky's editorial on page 1841.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cirrhosis is characterized by muscle wasting, malnutrition, and functional decline that confer excess mortality not well quantified by the Model for End‐Stage Liver Disease (MELD) Sodium (MELDNa) ...score. We aimed to develop a frailty index to capture these extrahepatic complications of cirrhosis and enhance mortality prediction in patients with cirrhosis. Consecutive outpatients listed for liver transplantation at a single transplant center without MELD exceptions were assessed with candidate frailty measures. Best subset selection analyses with Cox regression identified subsets of frailty measures that predicted waitlist mortality (=death or delisting because of sickness). We selected the frailty index by balancing statistical accuracy with clinical utility. The net reclassification index (NRI) evaluated the %patients correctly reclassified by adding the frailty index to MELDNa. Included were 536 patients with cirrhosis with median MELDNa of 18. One hundred seven (20%) died/were delisted. The final frailty index consisted of: grip strength, chair stands, and balance. The ability of MELDNa and the frailty index to correctly rank patients according to their 3‐month waitlist mortality risk (i.e., concordance‐statistic) was 0.80 and 0.76, respectively, but 0.82 for MELDNa+frailty index together. Compared with MELDNa alone, MELDNa+frailty index correctly reclassified 16% of deaths/delistings (P = 0.005) and 3% of nondeaths/delistings (P = 0.17) with a total NRI of 19% (P < 0.001). Compared to those with robust frailty index scores (<20th percentile), cirrhotics with poor frailty index scores (>80th percentile) were more impaired by gait speed, difficulty with Instrumental Activities of Daily Living, exhaustion, and low physical activity (P < 0.001 for each). Conclusion: Our frailty index for patients with cirrhosis, comprised of three performance‐based metrics, has construct validity for the concept of frailty and improves risk prediction of waitlist mortality over MELDNa alone. (Hepatology 2017;66:564–574).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The Liver Frailty Index (LFI), composed of 3 performance‐based tests (grip strength, chair stands, and balance), is a tool specifically developed in patients with cirrhosis to objectively measure ...physical function, a critical determinant of health outcomes. We aimed to (1) determine the range of LFI scores in adults with chronic liver disease but without cirrhosis, (2) determine the range of LFI scores in adults without known liver disease, and (3) evaluate reproducibility of the LFI in adults with cirrhosis listed for liver transplantation. Intraclass correlation coefficient (ICC) assessed interrater reliability of the LFI. Included were 91 adults with chronic liver disease, 109 adults without known liver disease, and 166 adults with cirrhosis with median Model for End‐Stage Liver Disease–sodium of 16. Median (interquartile range) LFI was 3.6 (3.1‐4.1) in adults with cirrhosis, 3.1 (2.5‐3.7) in adults with chronic liver disease but not cirrhosis, and 2.7 (2.2‐3.2) in adults without liver disease (P < 0.001). Using established LFI cutoffs for robust, prefrail, and frail categories, adults with cirrhosis or chronic liver disease were less likely to be robust (29% versus 53% versus 77%) and more likely to be prefrail (57% versus 42% versus 22%) or frail (14% versus 5% versus 1%) when compared with adults without liver disease (P < 0.001). The LFI had excellent reliability with ICC of 0.93 (95% confidence interval, 0.91‐0.95). In conclusion, the LFI has external validity in noncirrhotic populations and is highly reproducible among different raters. This objective assessment tool can be implemented in outpatient clinical practice or research to operationalize the concept of physical frailty.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Acute kidney injury (AKI) is a critical determinant of outcomes in hospitalized patients with cirrhosis, but little is known of the impact of AKI in the outpatient setting. We analyzed 385 adult ...outpatients with cirrhosis listed for liver transplant at a single center; excluded were those with severe hepatic encephalopathy, with hepatocellular carcinoma, or on hemodialysis. Baseline serum creatinine (bCr) was defined as the lowest value recorded, peak Cr as the highest value, ΔCr as peak Cr minus bCr, AKI as a rise in serum Cr (sCr) by ≥0.3 mg/dL from bCr, persistent kidney injury as elevation of sCR by ≥0.3 mg/dL from bCr on each subsequent clinical assessment. Among 385 outpatients with cirrhosis, bCr was ≤0.70, 0.70‐0.97, and ≥0.97 mg/dL in 28%, 38%, and 34%, respectively. At a median follow‐up of 16 (range 8‐28) months, 143 (37%) had one or more AKI episode, which increased significantly by bCr group (24% versus 37% versus 48%, P = 0.001). Of these 143 with AKI, 13% developed persistent kidney injury. A multivariable Cox regression analysis highlighted that bCr (hazard ratio HR, 2.96) and ΔCr (HR, 2.05) were the only factors independently associated with the development of persistent kidney injury (P < 0.001). The likelihood of death/delisting increased by bCr group (14% versus 19% versus 28%, P = 0.03). A competing risk analysis demonstrated that each 1 mg/dL increase in bCr was independently associated with a 62% higher risk of death/delisting when accounting for transplantation and adjusting for confounders. Conclusion: AKI is not only common in outpatients with cirrhosis but even “clinically normal” bCr levels significantly impact the risk of persistent kidney injury and waitlist mortality, supporting the need for a lower clinical threshold to initiate monitoring of renal function and implementation of kidney‐protective strategies.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The Short Physical Performance Battery (SPPB) is a well-established tool to assess lower extremity physical performance status. Its predictive ability for all-cause mortality has been sparsely ...reported, but with conflicting results in different subsets of participants. The aim of this study was to perform a meta-analysis investigating the relationship between SPPB score and all-cause mortality.
Articles were searched in MEDLINE, the Cochrane Library, Google Scholar, and BioMed Central between July and September 2015 and updated in January 2016. Inclusion criteria were observational studies; >50 participants; stratification of population according to SPPB value; data on all-cause mortality; English language publications. Twenty-four articles were selected from available evidence. Data of interest (i.e., clinical characteristics, information after stratification of the sample into four SPPB groups 0-3, 4-6, 7-9, 10-12) were retrieved from the articles and/or obtained by the study authors. The odds ratio (OR) and/or hazard ratio (HR) was obtained for all-cause mortality according to SPPB category (with SPPB scores 10-12 considered as reference) with adjustment for age, sex, and body mass index.
Standardized data were obtained for 17 studies (n = 16,534, mean age 76 ± 3 years). As compared to SPPB scores 10-12, values of 0-3 (OR 3.25, 95%CI 2.86-3.79), 4-6 (OR 2.14, 95%CI 1.92-2.39), and 7-9 (OR 1.50, 95%CI 1.32-1.71) were each associated with an increased risk of all-cause mortality. The association between poor performance on SPPB and all-cause mortality remained highly consistent independent of follow-up length, subsets of participants, geographic area, and age of the population. Random effects meta-regression showed that OR for all-cause mortality with SPPB values 7-9 was higher in the younger population, diabetics, and men.
An SPPB score lower than 10 is predictive of all-cause mortality. The systematic implementation of the SPPB in clinical practice settings may provide useful prognostic information about the risk of all-cause mortality. Moreover, the SPPB could be used as a surrogate endpoint of all-cause mortality in trials needing to quantify benefit and health improvements of specific treatments or rehabilitation programs. The study protocol was published on PROSPERO (CRD42015024916).
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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